The present invention relates to novel organoboron reagents which are useful in the preparation of unsubstituted propargylic alcohols.
Unsubstituted propargylic alcohols are important intermediates in the synthesis of a number of natural products, including the prostaglandins [Ann. N.Y. Acad. Sci. 180 38 1971, Prostaglandins 10 503 1975 and Ann. N.Y. Acad. Sci. 180 64 1971], steroids [J. Am. Chem. Soc. 99 8341 1977], carotenoids [J. Org. Chem. 41 3497 1976] and leukotrienes [J. Am. Chem. Soc. 106 3548 1984]. Unsubstituted propargylic alcohols are defined as those propargylic alcohols bearing a terminal hydrogen on the acetylenic functionality.
Propargylic alcohols have been prepared by a number of methods. The addition of alkynylmetals to aldehydes is one such method of preparing propargylic alcohols [Hebd. Seances Aced. Sci. 261 1992 1965, Bull. Soc. Chim. Fr. 205 1968, Hebd. Seances Aced. Sci., Seances Ser. C 289 1966, "Chemistry of Alkylenes "; Marcel Dekker: New York, 1969, Bull. Soc. Pharm. Bordeaux 101, 3 1962, J. Org. Chem. 38 3588 1973, Chem. Ber. 92 1270 1959, Chem. Ber. 92 541 1959, J. Am. Chem. Soc. 87 5632 1965, Bull. Soc. Chim. Fr. 1447 1957. These alkynylmetal reagents are highly basic and can cause unwanted base-induced eliminations. They are also highly nucleophilic and react with a variety of functional groups, thus restricting their versatility in the synthesis of complex organic molecules. In addition, except for the alkynyllithium, the preparation of alkynylmetals is often inconvenient due to the physical properties of the metals (i.e., flamability, reactivity, etc.). Also, in many cases, these metal complexes contain a number of alkyne ligands, but only successfully transfer one alkyne ligand.
Another method of preparing propargylic alcohols is the addition of B-1-alkynyl-9-borabicyclo[3.3.1]nonane reagents to aldehydes and ketones [J. Org. Chem. 50 1577 1985, J. Organometal. Chem. 131 163 1977]. These reagents are very mild and show no reactivity toward a variety of functional groups such as esters, nitriles, acetals, ketals, acid chlorides, alkyl halides, and amides. In contrast to the alkynylmetal reagents, the B-1alkynyl-9-borabicyclo[3.3.1]nonane reagents react cleanly with aldehydes and ketones to afford the corresponding propargylic alcohols. The B-1-alkynyl-9-borabicyclo[3.3.1]nonane reagents can also preferentially react with aldehydes in the presence of ketones and also demonstrate stereoselectivity [J. Organometal. Chem. 131 163 1977]. This reagent would have been useful in the preparation of a class of unsubstituted propargylic alcohols which are important synthetic intermediates in the synthesis of a number of natural products. Attempts to prepare B-ethynyl-9-borabicyclo[3.3.1]nonane, however, were unsuccessful [J. Organometal. Chem. 131 163 1977].
The novel organoboron reagents of the present invention are useful in the preparation of propargylic alcohols. These compounds react with aldehydes and ketones cleanly to afford propargylic alcohols in excellent yields and are useful in the preparation of a class of unsubstituted propargylic alcohols which are important synthetic intermediates in the synthesis of a number of natural products. Unlike the alkynylmetal reagents, the novel organoboron reagents of the present invention are convenient to prepare and can be stored as solutions at -40.degree. C. to -10.degree. C. for up to one week. The reagents can be isolated as 1:1 tetrahydrofuran complexes. These complexes are stable crystalline solids which have been stored at room temperature under an argon atmosphere for up to 6 months. In addition, the novel organoboron reagents of the present invention also demonstrate diastereomeric selectivity when reacted with enantiomerically pure aldehydes.